*Review* **Reviewing the Modern Therapeutical Options and the Outcomes of Sacubitril/Valsartan in Heart Failure**

**Diana-Carina Iovanovici <sup>1</sup> , Simona Gabriela Bungau 1,2,\* , Cosmin Mihai Vesa <sup>3</sup> , Madalina Moisi <sup>3</sup> , Elena Emilia Babes 4,\*, Delia Mirela Tit 1,2 , Tunde Horvath <sup>2</sup> , Tapan Behl <sup>5</sup> and Marius Rus <sup>4</sup>**


**Abstract:** Sacubitril/valsartan (S/V) is a pharmaceutical strategy that increases natriuretic peptide levels by inhibiting neprilysin and regulating the renin-angiotensin-aldosterone pathway, blocking AT1 receptors. The data for this innovative medication are mainly based on the PARADIGM-HF study, which included heart failure with reduced ejection fraction (HFrEF)-diagnosed patients and indicated a major improvement in morbidity and mortality when S/V is administrated compared to enalapril. A large part of the observed favorable results is related to significant reverse cardiac remodeling confirmed in two prospective trials, PROVE-HF and EVALUATE-HF. Furthermore, according to a subgroup analysis from the PARAGON-HF research, S/V shows benefits in HFrEF and in many subjects having preserved ejection fraction (HFpEF), which indicated a decrease in HF hospitalizations among those with a left ventricular ejection fraction (LVEF) < 57%. This review examines the proven benefits of S/V and highlights continuing research in treating individuals with varied HF characteristics. The article analyses published data regarding both the safeness and efficacy of S/V in patients with HF, including decreases in mortality and hospitalization, increased quality of life, and reversible heart remodeling. These benefits led to the HF guidelines recommendations updating and inclusion of S/V combinations a key component of HFrEF treatment.

**Keywords:** sacubitril/valsartan; mortality; morbidity; heart failure; ejection fraction
